Phase II study of gefitinib in metastatic or locoregionally recurrent nasopharyngeal carcinoma (NPC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 15509-15509
Author(s):  
A. T. Chan ◽  
B. Ma ◽  
E. P. Hui ◽  
A. King ◽  
M. Kam ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Growth Factor Receptor ◽  
Median Number ◽  
Molecule Inhibitor ◽  
Disease Stabilization ◽  
Recurrent Nasopharyngeal Carcinoma ◽  
Epidermal Growth ◽  
Grade 3

15509 Background: Our preclinical work has shown that epidermal growth factor receptor (EGFR) is expressed in ∼ 80% of undifferentiated NPC & gefitinib is a small molecule inhibitor against EGFR with anti-proliferative activity in NPC in vitro. Methods: We report the preliminary result of a phase II study of gefitinib in patients (pts) who progressed after 1–2 lines of chemotherapy (at least 1 line had to contain platinum) for metastatic or locoregionally recurrent NPC. Fourteen Chinese pts were accrued, of whom the median age was 48 years (range 34–64 years), 12 were males, 9 had metastatic & 5 had locoregionally recurrent NPC. All received gefitinib at 500mg/day orally, every 28 days with radiological assessment performed every 2 cycles for a maximum of 8 cycles. Ten pts had 1 line & 5 pts had 2 lines of prior chemotherapy. Results: The median number of administered cycles was 2 (range 1–8). Of the 14 pts evaluable for toxicity, the most commonly reported were acneiform rash (86%, grade 1–2, n = 10; grade 3, n = 4), dry skin (86%, grade 1–2), diarrhea (71%, grade 1–2), fatigue (64%, grade 1–2), anorexia (64%, grade 1–2) & nausea (20%, grade 2). Other grade 3–4 toxicities included fever (n = 2, skin cellulitis, infective pneumonia), hyponatremia (n = 2), near-syncope (n = 2), anemia (n = 1). Dose reduction to 250mg/day was required in 4 pts who encountered grade 3 skin rash. Of the 11 pts evaluable for response, 2 had stable disease (SD) for ≥ 6 months (m) (mean 6.8 m) 9 progressed and no partial responders. Five pts have died mostly of progressive disease & there were no treatment-related deaths. Conclusions: Gefitinib is well tolerated in pts with advanced NPC with some pts experiencing disease stabilization for over 6 months & study accrual is ongoing. No significant financial relationships to disclose.

Final results of AGITG ATTAX3 study: Randomized phase II study of weekly docetaxel (T), cisplatin, and fluoropyrimidine (F) with or without panitumumab (P) in advanced esophagogastric (OG) cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4081-4081 ◽  
Author(s):  
Niall C. Tebbutt ◽  
Timothy Jay Price ◽  
Katrin Marie Sjoquist ◽  
Anne-Sophie Veillard ◽  
Merryn Hall ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Growth Factor Receptor ◽  
Adverse Outcomes ◽  
Randomized Phase Ii ◽  
Safety Alert ◽  
Common Grade ◽  
Epidermal Growth ◽  
Grade 3 ◽  
Adeno Carcinoma

4081 Background: This randomized phase II study evaluated the efficacy and safety of P, a fully human mAb against the epidermal growth factor receptor combined with T-based chemotherapy in advanced OG cancer. Methods: Eligible pts had histologically confirmed metastatic OG cancer (adeno-carcinoma and squamous cell carcinoma) were ≥18 years of age, PS 0-2, with adequate renal, haematologic and liver function with measurable disease. All pts provided informed consent. Selection was not based on kras determination. Pts received T 30mg/m2 d1,8, C 60mg/m2 d1 and F; investigator choice of 5FU infusion 160mg/m2/d or capecitabine 500mg/m2bd continuous ±P 9 mg/kg d1 q3w. Treatment was administered for 8 cycles or until PD. The primary endpoint was response rate according to RECIST (1.1) assessed q6w. Planned enrolment target was 100 pts. Stratification variables included histology, PS and choice of F. Results: From April 2010 to November 2011, 77 pts were enrolled from 15 institutions. A safety alert from the REAL3 study (also involving P in OG cancer) prompted an unplanned review of data from ATTAX3 by the IDMC. The IDMC found no evidence of adverse outcomes associated with P, but as it did not appear that P would significantly improve efficacy, they recommended cessation of the study to new enrolment. Previously enrolled pts were treated and followed according to protocol. Median follow up is 24m. Treatment arms were well balanced; median age 59, 64y, male 77%, 87%, PS0-1 95%,90%, adenocarcinoma 90%,90%, capecitabine 67%, 66% for TCF/TCF-P, respectively. Common grade 3/4 toxicities include infection 18%,24%, febrile neutropenia 10%, 5%, anorexia 10%, 24%, nausea 18%,30%, stomatitis 3%,5%, diarrhoea 15%,24% , acneiform rash 0%, 8%, fatigue 18%, 30%, hypomagnesemia 10%, 16% for TCF/TCF-P. Efficacy outcomes are summarized in Table. Conclusions: The addition of P to T-based chemotherapy in advanced OG cancer did not improve efficacy and was associated with an increase in some toxicities. Clinical trial information: ACTRN12609000109202. [Table: see text]

Phase II Study of the Antibody Drug Conjugate Trastuzumab-DM1 for the Treatment of Human Epidermal Growth Factor Receptor 2 (HER2) –Positive Breast Cancer After Prior HER2-Directed Therapy

2011 ◽  
Vol 29 (4) ◽  
pp. 398-405 ◽  
Author(s):  
Howard A. Burris ◽  
Hope S. Rugo ◽  
Svetislava J. Vukelja ◽  
Charles L. Vogel ◽  
Rachel A. Borson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Growth Factor Receptor ◽  
Antibody Drug Conjugate ◽  
Her2 Positive ◽  
Epidermal Growth ◽  
Antibody Drug

Purpose The antibody-drug conjugate trastuzumab-DM1 (T-DM1) combines the biologic activity of trastuzumab with targeted delivery of a potent antimicrotubule agent, DM1, to human epidermal growth factor receptor 2 (HER2) –overexpressing cancer cells. Based on results from a phase I study that showed T-DM1 was well tolerated at the maximum-tolerated dose of 3.6 mg/kg every 3 weeks, with evidence of efficacy, in patients with HER2-positive metastatic breast cancer (MBC) who were previously treated with trastuzumab, we conducted a phase II study to further define the safety and efficacy of T-DM1 in this patient population. Patients and Methods This report describes a single-arm phase II study (TDM4258g) that assessed efficacy and safety of intravenous T-DM1 (3.6 mg/kg every 3 weeks) in patients with HER2-positive MBC who had tumor progression after prior treatment with HER2-directed therapy and who had received prior chemotherapy. Results With a follow-up of ≥ 12 months among 112 treated patients, the objective response rate by independent assessment was 25.9% (95% CI, 18.4% to 34.4%). Median duration of response was not reached as a result of insufficient events (lower limit of 95% CI, 6.2 months), and median progression-free survival time was 4.6 months (95% CI, 3.9 to 8.6 months). The response rates were higher among patients with confirmed HER2-positive tumors (immunohistochemistry 3+ or fluorescent in situ hybridization positive) by retrospective central testing (n = 74). Higher response rates were also observed in patients whose tumors expressed ≥ median HER2 levels by quantitative reverse transcriptase polymerase chain reaction for HER2 expression, compared with patients who had less than median HER2 levels. T-DM1 was well tolerated with no dose-limiting cardiotoxicity. Most adverse events (AEs) were grade 1 or 2; the most frequent grade ≥ 3 AEs were hypokalemia (8.9%), thrombocytopenia (8.0%), and fatigue (4.5%). Conclusion T-DM1 has robust single-agent activity in patients with heavily pretreated, HER2-positive MBC and is well tolerated at the recommended phase II dose.

A Phase II Study of Temsirolimus (CCI-779) in Patients with Advanced Leukemias.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4523-4523 ◽  
Author(s):  
Karen W.L. Yee ◽  
Guillermo Garcia-Manero ◽  
Deborah Thomas ◽  
Farhad Ravandi-Kashani ◽  
Srdan Verstovsek ◽  
...  
Keyword(s):  
Disease Progression ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Blast Crisis ◽  
Single Agent ◽  
Mammalian Target Of Rapamycin ◽  
Median Number ◽  
Prior Therapy ◽  
Flat Dose ◽  
Grade 3

Abstract Temsirolimus (CCI-779, Wyeth Pharmaceuticals) has been shown to inhibit proliferation of a variety of tumors and induce G1 cell cycle arrest by preventing activation of the serine/threonine kinase, mTOR (mammalian target of rapamycin), a downstream effector of the PI3K/Akt pathway. Several lines of evidence implicate the PI3K/Akt/mTOR pathway in hematological malignancies. Interim results of a phase II study evaluating the efficacy and toxicity of single-agent temsirolimus in patients with advanced malignancies are presented. Temsirolimus was administered weekly, at a flat dose of 25 mg, as a 30-minute intravenous infusion. Treatment was continued until evidence of disease progression or unacceptable toxicity. To date, 8 patients have been enrolled and 7 are evaluable for efficacy and toxicity (one patient did not receive temsirolimus). Of these 7 patients, 5 had AML, 1 CML-myeloid blast crisis, and 1 ALL. Median age was 68 years (range, 21 to 87 years) and 5 were male. All patients had received prior therapy, median 2 regimens (range, 1 to 3 regimens). The median number of temsirolimus doses administered was 3 (range, 1 to 10) with a median time on study of 18 days (range, 3 to 89+ days). The most common temsirolimus-related adverse events were grade ≤ 2 and consisted of anorexia, nausea and/or vomiting and diarrhea, mucositis, dermatitis, hypertriglyceridemia, hyperglycemia, hypomagnesemia, hypocalcemia, hypokalemia, hypophosphatemia, and fatigue/asthenia. No patient developed nonspecific pneumonitis. Grade 3 toxicities included fatigue/asthenia (2), hyperglycemia (1), painful mucositis with dehydration and electrolyte abnormalities (1), diarrhea with hypokalemia (1), and hypophosphatemia (1). No patient experienced grade 4 toxicities or death from temsirolimus. No patient required dose reductions, but 2 did have dose delays due to grade 3 mucositis (1) and out-of-state hospitalization for pneumonia and atrial fibrillation (1). No patient achieved a complete remission. One patient with heavily pre-treated Philadelphia-negative precursor B-cell ALL had a transient 79% to 91% reduction in peripheral blood blasts 4 days after the first dose of temsirolimus that was maintained for 12 days prior to disease progression with involvement of the synovial fluid in bilateral knees. At the time of analysis, 6 of the 7 patients have discontinued treatment due to disease progression (4), patient refusal (1), or physician decision (1). Preliminary findings indicate that temsirolimus is relatively well-tolerated at a dose of 25 mg per week and may have biologic activity in ALL. Accrual onto the study is currently ongoing.

Erlotinib Is Not Effective In Patients (Pts) With JAK-2 V617F Positive Polycythemia Vera

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1597-1597
Author(s):  
Mohamad Cherry ◽  
Mohamad Khawandanah ◽  
Zhizhuang Joe Zhao ◽  
Samer A Srour ◽  
Howard Ozer ◽  
...  
Keyword(s):  
Polycythemia Vera ◽  
Conflicts Of Interest ◽  
Growth Factor Receptor ◽  
Median Number ◽  
Preclinical Study ◽  
Spleen Size ◽  
University Of Oklahoma ◽  
Grade 3

Abstract Introduction Erlotinib is an epidermal growth factor receptor small-molecule inhibitor and is FDA approved for the treatment of lung and pancreatic cancers. In preclinical study, in vitro colony culture assays revealed that erlotinib at micro-molar concentrations effectively suppressed the growth and expansion of Polycythemia Vera (PV) hematopoietic progenitor cells while having little effect on normal cells. Several JAK inhibitors are being studied for the management of PV, one of which has been approved for the treatment of myelofibrosis (ruxolitinib). Aim To study the clinical effect of erlotinib in pts diagnosed with JAK2V617F + PV. Methods We conducted a single arm, prospective phase II study at the University of Oklahoma and the Oklahoma City VA hospitals in pts with WHO defined JAK-2 V617F positive PV from June 2010 to August 2012. Appropriate IRB approval was obtained in accordance with Hilsinki declaration. Pts had to be requiring phlebotomy. Toxicity was assessed by treating physicians using NCI version 4. Dose modification for erlotinib was done using label recommendations. Results Five Caucasian pts were enrolled (3 (60%) males, with median age at enrollment of 63 years, range 26-79). Pts had pretreatment median hemoglobin14.4 g/dL (10.4 -19.2 g/dL), median platelet count 511 x109 (424-681 x109), median white blood cell (WBC) 14.4 x109(7.8- 18.3 x109). Three pts had splenomegaly prior to treatment. Median number of prior pharmacologic treatments (hydroxyurea, anagralide or interferon) was 1, range 0-2. Pts were given erlotinib 150 mg orally daily for 16 weeks: responders (phlebotomy free or decrease in spleen size) were allowed to continue a total of 1 year of treatment, while non-responders were taken off the study. Three (60%) patients received therapy for 16 weeks and did not achieve hematological response or improvement in spleen size. Two (40%) pts were taken off the study after 2 doses secondary to severe toxicities (grade 3 colitis in 1 case, and grade 3 facial rash in 1case). No therapy continued beyond 16 weeks (due to toxicity or lack of response). All pts in the study developed rash (grade 1 – 3) and diarrhea (grade 1 – 2). Three pts developed mucositis (see Table 1). No death was observed during the study and follow up period (median follow up was 23 months, range 12-37 months). Study was closed due to lack of efficacy. Conclusions Despite in vitro efficacy of erlotinib as potent inhibitor of JAK-2 activity, erlotinib is not effective in pts with JAK-2 V617F positive PV with poor toxicity profile. Poor accrual was related to potential toxicity of erlotinib compared to alternative treatments in view of lack of clinical efficacy. Disclosures: No relevant conflicts of interest to declare.

Incorporation of bevacizumab (B) and erlotinib (Er) with induction (Ind) and concurrent (Conc) carboplatin (Cb)/paclitaxel (P) and 74 Gy of thoracic radiotherapy in stage III non-small cell lung cancer (NSCLC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 7528-7528
Author(s):  
M. A. Socinski ◽  
T. E. Stinchcombe ◽  
J. S. Halle ◽  
D. T. Moore ◽  
W. J. Petty ◽  
...  
Keyword(s):  
Growth Factor ◽  
Phase Ii ◽  
Growth Factor Receptor ◽  
Conformal Radiotherapy ◽  
Vascular Endothelial ◽  
Treatment Paradigm ◽  
Epidermal Growth ◽  
Grade 3 ◽  
Endothelial Growth Factor ◽  
Pet Scans

7528 Background: Therapies directed at both the epidermal growth factor receptor (EGFR) and the vascular endothelial growth factor (VEGF) pathways have been shown to improve survival in NSCLC and also have radiosensitizing properties. Methods: Pts receive Ind Cb (AUC 6), P (225 mg/m2) and B (15 mg/kg) on d1 and 22. PET scans are done pre- and post-I. On day 43, pts receive weekly Cb (AUC 2 x 7) and P (45 mg/m2 x 7) with 74 Gy (2 Gy/d) of thoracic conformal radiotherapy (TCRT). Cohort I (n=5) received B at 10 mg/kg q2wks during C therapy. Cohorts II and III (both n=5) received the same dose of B as in cohort I but also received Er at 100 mg and 150 mg po Tuesday - Friday of each week of C therapy, respectively. The primary endpoint is PFS at 1 year. All histologies are allowed including squamous (SQ) (an early stopping rule is in place for pulmonary hemorrhagic (PH) complications in SQ pts). Results: Thus far, 31 eligible PS 0–1 pts have been accrued (med age 62 yrs, range 41–74, 19 non- squamous, 12 SQ, 63% IIIA, 37% IIIB). Ind CbP + B has been well tolerated (1 gr 3 hypertension). No PH during Ind has been seen (including the 12 SQ cell pts). Response after Ind, 37% PR, 59% SD, 4% PD. Tumor volumes and PET SUVs have significantly decreased comparing pre- and post-Ind studies (p=0.0001 and p=0.0002, respectively). Cohort II has been expanded as the phase II regimen. To date, 25 of 26 (96%) pts have achieved the dose of 74 Gy (1 pt stopped at 60 Gy due to ILD). During Conc therapy, the principal toxicity has been esophagitis (53.8% gr 2, 19.2% gr 3). One grade 3 PH occurred in 1 SQ pt. One gr 5 late (> 2 mos after treatment) PH occurred in a SQ pt. Overall response rate following treatment - 68.2% (95% CI, 45–86%). The PFS at 1 year is 58% (95% CI, 34–76%) with an estmated 1-year overall survival rate of 79% (95% CI, 53–92%) which compares favorably to our historical experience. Conclusions: Preliminarily, we conclude that 1) Incorporation of B and E into this treatment paradigm appears feasible, 2) Esophagitis remains the primary toxicity, 3) Phase II accrual continues but early analysis of survival appears promising. Further details regarding the TCRT parameters and toxicity will be presented. [Table: see text]

Novel organic arsenic molecule darinaparsin: Development of IV and oral forms

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8501-8501 ◽  
Author(s):  
I. Lossos ◽  
M. D. Craig ◽  
M. S. Tallman ◽  
R. V. Boccia ◽  
P. R. Conkling ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Complete Response ◽  
Median Number ◽  
Two Phase ◽  
Phase I Studies ◽  
Advanced Malignancies

8501 Background: Darinaparsin (ZIO-101) is a novel organic arsenical active against diverse cancers in vitro, and in vivo. Darinaparsin i.v. activity in lymphoma is being evaluated in a phase II study. Darinaparsin is orally bioavailable; the oral form is being investigated in two phase I studies in patients with advanced malignancies. Methods: Phase II trial is being conducted in patients diagnosed with advanced lymphomas who had ≥ 1 prior therapy. Patients receive 300 mg/m2/day of darinaparsin i.v. for 5 consecutive days every 28 days. Efficacy and safety are evaluated by standard criteria. Phase I oral dose escalation studies are being conducted in patients with advanced malignancies and explore safety, MTD, DLTs and preliminary efficacy of continuous and intermittent dosing schedules. Starting continuous dose is 100 mg BID for 3 weeks with 1 week rest, starting intermittent dose is 300 mg twice weekly for 3 weeks followed by 1 week rest. Results: The phase II study has accrued 28 lymphoma patients (21 non-Hodgkin's, 7 Hodgkin's); median age at baseline 61 years, ECOG ≤2, median number of prior therapies 3. Seventeen subjects have received at least 2 cycles of darinaparsin and are evaluable for efficacy. Of these, 1 subject (PTCL) has achieved a complete response, 3 - partial responses (2 marginal zone, 1 Hodgkin's), and 4 stable disease (2 PTCL, 1 DLBCL, 1 Hodgkin's). A total of 63 cycles of darinaparsin have been administered to subjects with lymphoma. No Gr. 3 or higher drug-related AEs were reported. Two SAEs were considered possibly drug-related (fall; neutropenic fever). Phase I studies accrued 35 patients; median age at baseline 58 years, ECOG ≤2, median number of prior therapies 3. Predominant tumor types include: colorectal (17), pancreatic (3), NHL (3). Current darinaparsin dose levels: continuous 200 mg BID, 2× weekly 900 mg. Of 18 patients evaluable for efficacy, 10 demonstrate SD ≥ 3 cycles. Oral darinaparsin bioavailability is 58%. Drug-related AEs include nausea/vomiting, fatigue, decreased appetite/anorexia. Conclusions: Darinaparsin is active in heavily pretreated patients with advanced lymphoma and has been very well tolerated. Oral darinaparsin is also well tolerated, and shows early activity. [Table: see text]

Phase II study of temozolomide in combination with topotecan (TOTEM) in relapsed or refractory neuroblastoma and other pediatric solid malignancies: A European ITCC study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 9517-9517
Author(s):  
Angela Di Giannatale ◽  
Kieran Mc Hugh ◽  
Nathalie Dias ◽  
Annick Devos ◽  
Birgit Geoerger ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Phase Ii ◽  
Topoisomerase I ◽  
Phase Ii Study ◽  
Alkylating Agents ◽  
Objective Response ◽  
Progression Free Survival ◽  
Tumor Control ◽  
Disease Stabilization ◽  
Grade 3

9517 Background: Temozolomide and topotecan have shown activity in several pediatric cancers, including neuroblastoma. Resistance to alkylating agents due to MGMT expression, MMR deficiency or microsatellite instability may be overcome through the combination with topoisomerase I inhibitors. The combination of temozolomide and topotecan (TOTEM) was well tolerated and showed preliminary activity in children with neuroblastoma and glioma (Rubie et al, 2010). Methods: This multicenter, non-randomized, multi-cohort Phase II study included children with neuroblastoma according to a 2-stage Simon design, and patients with central nervous system (CNS) and extra-cranial solid tumors in a descriptive design. Temozolomide was administered orally at 150 mg/m2 followed by topotecan at 0.75 mg/m2 intravenously for 5 consecutive days every 28 days. The main endpoint was objective response (OR), i.e., Complete or Partial Response (CR+PR), evaluated after 2 cycles according to WHO criteria, or INRC criteria for neuroblastoma patients with mIBG-positive lesions, by an independent radiological review. Independent review of mIBG imaging is pending. Results: 103 patients, median age 9.4 years (range 1-21), were treated between June 2009 and May 2011 in 18 centers: 38 neuroblastoma, 33 CNS tumors and 32 other solid tumors. Overall 420 cycles were administered (median 3 per patient; range 1-12). Grade 3 or 4 neutropenia was frequent (55% courses), though only 6% of patients developed febrile neutropenia. In the neuroblastoma cohort, 1 CR and 7 PR were observed, leading to an estimated OR rate of 21% (95%CI, 10-37%). Additionally 22 patients had disease stabilization (SD), leading to an overall tumor control (CR+PR+SD) of 79% (63-90%), and a 12-month progression-free survival rate of 47% (31-64%). Overall, 17/102 evaluable patients achieved an OR (17%, 10-25%), with 1 CR and 3 PR in 9 medulloblastoma (44%, 14-79%), 2 PR in 4 PNET, 1 PR in 12 malignant glioma, and 2 PR in 9 RMS. Conclusions: Temozolomide-topotecan combination results in significant tumor control in children with neuroblastoma and medulloblastoma/PNET with favorable toxicity profile.

A phase II study of afatinib in patients (pts) with metastatic human epidermal growth factor receptor (HER2)-positive trastuzumab-refractory esophagogastric (EG) cancer.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 52-52 ◽  
Author(s):  
Yelena Yuriy Janjigian ◽  
Marinela Capanu ◽  
Tooba Imtiaz ◽  
David Paul Kelsen ◽  
Geoffrey Yuyat Ku ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Tumor Regression ◽  
Growth Factor Receptor ◽  
Standard Of Care ◽  
Cancer Resistance ◽  
Her2 Positive ◽  
Tumor Biopsy ◽  
Disease Stabilization ◽  
Erbb Family Blocker

52 Background: Trastuzumab (T) combined with chemotherapy has been the standard of care for pts with HER2+ EG cancer. Resistance to T is now emerging in this population. Afatinib (A), a potent ErbB Family Blocker, induced nearly complete tumor regression in MSKCC HER2+ patient derived xenografts (PDX). We report the initial results of a phase II study of afatinib in patients with T refractory EG cancer. Methods: Pts with HER2+ (IHC 3+ or FISH>2.0) EG adenocarcinoma –progressive on trastuzumab -received A 40 mg. Archival pre-T tissue, tumor biopsy after progression on T and after 1 week on A mandated on protocol. The primary endpoint-overall clinical benefit at 4 months: stable disease (SD) or partial response (PR). Results: 14 pts treated with A; median duration 5.1 mos (1.7 to 12.1 mos). Median age 62, KPS 80, median 2 (1 to 4) prior T containing regimens, 64% of tumors IHC3+; 36% IHC2+/FISH>2.2. Adverse events included: diarrhea (Grade 1/2:69%), fatigue (Grade 1/2:54%), rash (Grade 1/2:54%), mucositis (Grade 1:23%), paronychia (Grade 1/2:15%). To date, 13 pts evaluable for response, 3 of 13 pts (23%) had disease stabilization (PR or SD); 1 pt with confirmed PR - a durable 75% regression of biopsy proven metastases. Median OS 6.6 mos (1.9 to NR). PDXs established from biopsies of T refractory tumors of 5 pts. Next generation sequencing of matched pre-T and post-T progression tumors from 6 pts was performed and results will be reported. Conclusions: Afatinib shows clinical efficacy in patients with T refractory EG cancer. The study has been expanded to accrue additional patients. Efforts to elucidate the mechanisms of T resistance including validation of potential drivers of T resistance using HER2+ PDXs are ongoing. Updated molecular and clinical data will be presented. Clinical trial information: NCT01522768.

Phase II study of pazopanib with weekly paclitaxel in refractory urothelial cancer.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 294-294 ◽  
Author(s):  
Sandy Srinivas ◽  
Sujata Narayanan ◽  
Lauren Christine Harshman ◽  
Russell Kent Pachynski ◽  
Anthony P. Lam ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Performance Status ◽  
Progression Free Survival ◽  
Median Number ◽  
Upper Urinary Tract ◽  
Weekly Paclitaxel ◽  
Moderate Activity ◽  
Ecog Performance Status ◽  
Grade 3

294 Background: Currently, there are no standard treatments for relapsed or refractory urothelial carcinoma (UC). Discouraging results have been observed in trials evaluating established chemotherapeutics as single agents or in combination regimens. Paclitaxel has moderate activity when used alone and in combination in UC. Pazopanib is active in other solid tumors secondary to its potent anti-angiogenic effects. We report the results of a multi-center phase II study evaluating the combination of paclitaxel with pazopanib in refractory UC. Methods: Eligible patients (pts) had histologically confirmed UC, with disease that progressed on upto 2 chemotherapeutic regimens. Pazopanib (800 mg) was administered daily, with weekly paclitaxel (80mg/m2) for 3 weeks in a 28 day cycle. Treatment was continued until disease progression or unacceptable toxicity. The primary endpoint of the study was response-rate (RR) based on RECISTv 1.1 criteria. Secondary endpoints included safety, and progression free-survival (PFS). Results: From April 2010 to September 2014, 32 patients were enrolled. Median age was 67 years (29-89) and median ECOG performance status was 1 (0-2). 17 pts (54%) had UC of the upper urinary tract disease and 15(47%) had primary bladder tumors. All pts had multiple metastatic sites, including 9 (28%) with liver metastases. Median number of prior cytotoxic regimens was 2, and 50% were considered cisplatin responsive. Objective responses were observed in 58% with 3 (12%) complete responses (CR), and 12 pts (46%) with partial responses (PR). Another 9 (35%) acheived stable disease (SD). High grade toxicities included grade 3 hypertension (n=2), grade 3 fatigue (n=4), grade 3 thrombosis (n=2) and grade 4 neutropenia (n=2). Nearly half of the patients( n= 14 ) required growth factor support. Conclusions: Our phase II study combining paclitaxel and pazopanib demonstratedsignificant anti-tumor activity in relapsed/refractory UC. This combination is safe, effective and is worthy of evaluation in randomized phase 3 study. Clinical trial information: NCT01108055.

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